How the body metabolizes next-generation anti-androgen agents affects their anti-tumor activity in the treatment of prostate cancer, according to recent preclinical research. These results might improve the treatment of resistant, aggressive prostate cancer.

Next-generation anti-androgens decrease the supply of the male hormone androgen to prostate tumors, thereby decreasing tumor proliferation. Patients who receive the drugs have tumors that are resistant to hormone-deprivation therapy, and anti-androgens have improved survival in patients with advanced disease. However, patients can eventually become resistant to these medications.

This study examined galeterone, a steroidal anti-androgen previously examined in a clinical trial setting. Results showed that the metabolism of galeterone converts it to D4G, an intermediate molecule that inhibits the synthesis of androgen and decreases the amount of androgen available to tumors. However, galeterone is also metabolized to a tumor-proliferative compound.

Another anti-androgen, abiraterone, is metabolized into D4A, and abiraterone's metabolite D4A has greater anti-tumor activity than abiraterone alone.

These combined results suggest that the efficacy of steroidal anti-androgens should be carefully examined for all effects on tumors.

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